A history of alternative reinforcement reduces stimulus generalization of ethanol-seeking in a rat recovery model

Abstract

Background: Longer periods of recovery reduce the likelihood of relapse, which may be due to a reduced ability of various stimuli to occasion alcohol or drug seeking. However, this hypothesis remains largely uninvestigated.

Methods: Here we assessed the ability of intermediate stimuli to occasion responding for ethanol in rats trained to discriminate an 8 kHz tone signaling a food fixed-ratio (FR) of 5 and an ethanol FR5, from a 16 kHz tone signaling a food FR150 and ethanol FR5. In the presence of the 8 kHz tone responding for food predominates, and in the presence of the 16 kHz tone, responding for ethanol predominates.

Results: In the context of alternation between these conditions, varying the tone from 8 to 16 kHz produces a graded increase in ethanol (versus food) responding, consistent with a stimulus generalization function. A recent history of responding under food-predominant choice conditions, either during the test session or in the four sessions that precede it shifts the generalization function downwards. Extending this history to nine sessions shifts the curve further downwards. The stimulus generalization function was similar in a separate group, trained with different relative ratios for food and ethanol, but with similar behavioral allocation under each discriminative stimulus. Finally, withholding access to food and ethanol for 4 or 16 sessions did not affect the stimulus generalization gradient.

Conclusion: These results suggest that longer histories of reinforced alternative behavior might reduce the likelihood of relapse by decreasing the control exerted over alcohol- or drug-seeking by stimuli similar to those that previously occasioned alcohol- or drug-seeking.

Figure 1

Effect of conditions during the test session on the stimulus generalization function. Stimulus generalization functions generated during a test session in which conditions during reinforced components alternated (open circles, solid line) between an 8kHz tone signaling food FR5 and ethanol FR5 (food-predominant) and a 16kHz tone signaling food FR150 and ethanol FR5 (ethanol-predominant) or were only food-predominant conditions (solid triangles, dashed line). Test sessions were conducted after four preceding sessions in which conditions alternated. Points show the mean percent ethanol responding (left axis) and food responding (right axis) for 5 rats during presentation of each tone indicated on the abscissa. Bars represent the standard error of the mean, and lines represent the sigmoidal function. Some points have been nudged along the abscissa for clarity.

Figure 2

The effect of a history of responding under only the food -predominant condition on the stimulus generalization function. All stimulus generalization functions were generated during a test session with alternating (between food-predominant and ethanol-predominant conditions) reinforced components. The function generated following four preceding sessions of alternating conditions is reproduced from Figure 1 (open circles, solid lines). The function determined after four preceding sessions of responding only under food -predominant conditions is shown by the upright triangles and dashed line, and after nine preceding sessions of responding under only food -predominant conditions by the downward triangles and dotted line. Points represent the mean ± S.E.M. Lines represent the sigmoidal function fitted to each data set. All points represent data from five rats except for the downwards triangle which represents four rats. Some points have been nudged along the abscissa for clarity.

Figure 3

Effect of conditions during the test session on stimulus generalization functions generated following 9 preceding session of responding under only food -predominant conditions. The function generated during a test session with alternating (between food-predominant and ethanol-predominant conditions) reinforced components is represented by the downward facing triangles and dotted line, redrawn from Figure 2. The function generated during a test session in which only food predominant conditions were present during reinforced components is represented by the squares and dashed line. Points represent the mean ± S.E.M for 5 rats. Lines represent the sigmoidal function fitted to each data set. Some points have been nudged along the abscissa for clarity.

Figure 4

Effect of different relative response requirements for food and ethanol on the stimulus generalization function. The stimulus generalization function generated in rats responding under food FR150/ethanol FR5 and food FR5/ethanol FR5 during a test session with alternating reinforced components following four sessions of alternating contingency conditions is reproduced from Figure 1 (open circles, solid lines). This function is compared with the function generated in a separate group of 5 rats responding under food FR75/ethanol FR5 and food FR25/ethanol FR5 contingencies (triangles, dashed line). Points represent the mean ± S.E.M for 5 rats. Lines represent the sigmoidal function fitted to each data set. Some points have been nudged along the abscissa for clarity.

Figure 5

Effect of suspending training on the stimulus generalization function. The stimulus generalization function generated following four sessions of alternating contingency conditions in rats responding under food FR75/ethanol FR5 and food FR150/ethanol FR5 conditions is reproduced from Figure 4 (open triangles, dashed line). This function is compared with the function generated following suspended training for the equivalent of 4 or 16 sessions (filled triangles, dashed and dotted lines). Points represent the mean ± S.E.M for 5 rats. Lines represent the fitted model for each function. Some points have been nudged along the abscissa for clarity.